title: The role of CYP2C8 genotypes in dose requirement  and levels of everolimus after heart transplantation.
abstract: Everolimus is an immunosuppressive drug metabolized by enzymes of the CYP family. A common variant of the CYP2C8 gene, CYP2C8*3, results in strongly decreased CYP2C8 activity, but its role for the pharmacogenetics of everolimus remains unclear. Aim of the present study was to examine the role of CYP2C8 variants in everolimus dose and drug levels after heart transplantation. The present study comprised 30 patients with everolimus based maintenance therapy after heart transplantation. CYP2C8 genotypes were determined and correlated with clinical data. In all, 21 subjects carried the CYP2C8 *1/*1 genotype and 9 subjects carried the CYP2C8 *1/*3 genotype. Neither everolimus dose nor everolimus levels were associated with CYP2C8 genotype at any point of time (p < 0.05). During follow-up, graft rejection reactions were observed in two patients and infections were observed in seven patients. In one patient, type 2 diabetes was diagnosed during follow-up. None of these adverse events were significantly associated with CYP2C8 genotypes. We conclude that in adult patients after heart transplantation, CYP2C8 genotypes are not associated with dose requirements or levels of everolimus.
authors.affiliation: Department of Surgery, Division of Transplantation, Medical University Graz, Auenbruggerplatz 29, 8036 Graz, Austria. daniela.kniepeiss@medunigraz.at
authors.forename: Daniela
authors.initials: D
authors.lastname: Kniepeiss
authors.forename: Doris
authors.initials: D
authors.lastname: Wagner
authors.forename: Andrä
authors.initials: A
authors.lastname: Wasler
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Tscheliessnigg
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood* / Q000235:genetics*; D065727:Cytochrome P-450 CYP2C8; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D020123:Sirolimus